oncogenes

..e. the 'Achilles' heel,' in specific cancers. Finally, we discuss the use of molecular targeted agents in combination with other anticancer agents as a strategy to optimize therapy and prevent disease recurrence...

..switch places the emphasis on producing intermediates for cell growth and division, and it is regulated by both oncogenes and tumor suppressor genes in a number of key cancer-producing pathways...

In cancer cells, genetic alterations can activate proto-oncogenes, thereby contributing to tumorigenesis. However, the protein products of oncogenes are sometimes overexpressed without alteration of the proto-oncogene...

..They show that miR-34a suppresses brain tumor growth by targeting c-Met and Notch. The results also suggest that miR-34a could serve as a potential therapeutic agent for brain tumors...

..In addition, some miRNAs may function as oncogenes or tumor suppressors...

..Linking pathway deregulation with sensitivity to therapeutics that target components of the pathway provides an opportunity to make use of these oncogenic pathway signatures to guide the use of targeted therapeutics...

..Together, these studies indicate that non-coding RNAs, specifically microRNAs, can modulate tumour formation, and implicate the mir-17-92 cluster as a potential human oncogene...

..e., the "Achilles heel") in specific cancers. Combination therapy may also be required to prevent the escape of cancers from a given state of oncogene addiction...

..Similar checkpoint responses were induced in cultured cells upon expression of different oncogenes that deregulate DNA replication...

..Yet recent experimental findings suggest that, in both precancerous lesions and cancers, activated oncogenes induce stalling and collapse of DNA replication forks, which in turn leads to formation of DNA DSBs...

..There are sequence homologies to human epidermal growth factor receptor and the members of the src family of oncogene products...

..The purposes of this review are to highlight examples of progress in these areas, indicate where knowledge is scarce and point out fertile grounds for future investigation...

..The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism...

..We provide a general overview of the mechanisms of oncogene activation and the functions of oncogenes. Lastly, we review oncogenic events in melanoma.

..These results indicate that heterochromatin induced by oncogenic stress restrains DDR and suggest that the use of chromatin-modifying drugs in cancer therapies may benefit from the study of chromatin and DDR status of tumours...

Breast cancer progression involves multiple genetic events, which can activate dominant-acting oncogenes and disrupt the function of specific tumor suppressor genes...

..This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation...

..In a screen for miRNAs that cooperate with oncogenes in cellular transformation, we identified miR-372 and miR-373, each permitting proliferation and tumorigenesis ..

..The aim of this review is to highlight the molecular relationship between the control of cell polarity and the regulation of cell motility during oncogenesis...

..Thus pRb and/or pRb-like proteins likely mediate both p53-dependent and p53-independent responses to radiation...

..This similarity suggests a mechanism for transformation by SSV and other agents, involving expression of growth factors...

..We discuss such synergy with respect to the cooperating oncogenes MYC, RAS and BCL2.

Several oncogenes and tumor-suppressor genes have been shown to be implicated in the development, progression and response to therapy of invasive breast cancer...

Different fusion oncogenes in acute myeloid leukemia (AML) have distinct clinical and laboratory features suggesting different modes of malignant transformation...

..of tumor origin and behavior, they are causally linked to the emergence and development of cancer by acting as oncogenes or tumor suppressors...

..Because amplified regions often harbor oncogenes and/or other tumor-associated genes, and because 9p23-24 amplification had been reported in various other types ..

..This review will focus on integrating current models and will highlight data that provide new insight into the signals that function to suppress human tumor development...

Lung cancer is a leading cause of cancer death, where the amplification of oncogenes contributes to tumorigenesis. Genomic profiling of 128 lung cancer cell lines and tumors revealed frequent focal DNA amplification at cytoband 14q13...

..autophagic cell death signals in response to various cellular stresses including the misregulated expression of oncogenes in pre-malignant cells...

..One-third of these loci affected breast cancer oncogenes, whose amplifications were validated with specific probes: 17q12 (two cell lines with ERBB2 amplifications), ..

..consists in sensing and reacting to DNA damage through the ATM/ATR and Chk1/Chk2 kinases, and "policeman of the oncogenes" that, correspondingly, consists in responding to oncogenic signaling through the p53-stabilizing protein ARF...

..The mechanism by which v-sis transforms cells could involve the constitutive expression of a protein with functions similar or identical to those of a factor active transiently during normal cell growth...

Multiple oncogenes (in particular phosphatidylinositol 3-kinase, PI3K; activated Akt1; antiapoptotic proteins from the Bcl-2 family) inhibit autophagy...

....

..insertional mutagenesis has been proposed as an efficient mechanism to turn on or to increase the expression of oncogenes in several avian or mammal models...

..Intriguingly, bypassing oncogene-induced senescence by inactivation of p53 and Rb did not eliminate the accumulation of oncogene-induced DNA damage foci (ODDI), suggesting a mechanism that may limit transformation in immortalized cells...

..We studied hEag1 gene expression and its regulation by estradiol, antiestrogens, and human papillomavirus (HPV) oncogenes (E6/E7)...

..Thus, the ASPP family of proteins helps to determine how cells choose to die and may therefore be a novel target for cancer therapy...

....

Transformation by tyrosine kinase oncogenes (TKOs) in myeloid malignancies, including BCR-ABL in chronic myeloid leukemia, FLT3ITD in acute myeloid leukemia or JAK2V617F in myeloproliferative neoplasms, is associated with increased ..

Dysregulation of oncogenes by translocation to the IgH locus (14q32) is a seminal event in the pathogenesis of B-cell tumours. In multiple myeloma (MM), translocations to the IgH locus have been reported at an incidence of 20-60%...

..This data suggests that perforin may mediate some suppression of epithelial carcinogenesis by intervening early in the tumor development process...

..This region contains the transactivation domain of p53, suggesting that mdm-2 may inhibit p53 function by disrupting its interaction with the general transcription machinery...

..We will discuss how and under what circumstances oncogenes and epigenetic factors modify CLU expression, with important consequences for mammalian tumorigenesis.

..Furthermore, we identified two viral oncogenes, v-cyclin and v-Bcl2, that are critical to EC survival and that modify EC proliferation and survival during ..

..These results indicate that CDC5L, a cell cycle regulator important for the G2-M transition, is the most likely candidate oncogene for the 6p12-p21 amplicon found in osteosarcoma...

..Clinically, amplification has prognostic and diagnostic usefulness, and is a mechanism of acquired drug resistance...

In late 1990s, it was shown that activated oncogenes are able to induce senescence. Since then large leaps in understanding this phenomenon have been achieved...

..is also rapidly induced by the polypeptide growth factor epidermal growth factor, providing a new link between oncogenes and growth factors...

..HPV16 encodes three oncogenes: E5, E6, and E7...

..Here we discuss the possibility that early ATL cells are Tax-oncogene-addicted while late ATL cells are oncogenic microRNA (oncomiR) - addicted. The potential utility of interrupting oncomiR addiction as a cancer treatment is broached...

..p12 has been found in 13%-29% of high-grade osteosarcomas, suggesting the presence of an oncogene or oncogenes that may contribute to their development...

..Our results thus identify let-7a-3 as an epigenetically regulated miRNA gene with oncogenic function and suggest that aberrant miRNA gene methylation might contribute to the human cancer epigenome...

..Our observations suggest PIK3CA is an oncogene that has an important role in ovarian cancer...

..Thus, senescence in human preneoplastic lesions is a manifestation of oncogene-induced DNA replication stress and, together with apoptosis, provides a barrier to malignant progression...

..To date, most genome-wide array comparative genomic hybridization studies have used tumor panels of relatively large tumor size and high Nottingham Prognostic Index (NPI) that are not as representative of breast cancer demographics...

..Mammary cells lacking oncogenic transgenes displayed a similar capacity for long-term residence in the lungs but did not form ectopic tumors...

..In the January issue of Nature Medicine, Thomas et al. identify the loss of VHL tumor suppressor gene as a potential determining factor in tumor sensitivity to rapamycin...

..The method consistently ranked the known gene in the top 20 (0.3%), outperforming conventional approaches in 3 of 4 cases...

..analyses delineated cIAP1, a known inhibitor of apoptosis, and Yap, a transcription factor, as candidate oncogenes in the amplicon...

..How these proteins control centrosome duplication and function, and how their mutational activation and/or inactivation results in numeral and functional centrosome abnormalities, is discussed in this Review...

..Thus, high-level expression of the HPV-16 E6 protein in differentiating keratinocytes directly alters expression of genes that influence host resistance to infection and immune function...

..Thus, losing miRNA-directed repression of an oncogene provides a mechanism for tumorigenesis, and disrupting a single miRNA-target interaction can produce an observable phenotype in mammalian cells...

..malignancies and suggests a causal role of microRNAs in neoplasia, presumably because microRNAs can function as oncogenes or tumor suppressors...

..This first in vitro model system faithfully recapitulating the development of EOCs using normal human OSE cells should greatly facilitate further studies of EOCs...

Cancer is a multistep process whereby genetic events that result in the activation of proto-oncogenes or the inactivation of tumor suppressor genes usurp physiologic programs mandating relentless proliferation and growth...

..These findings suggest that while certain members of the E2F family may positively regulate cell cycle progression, E2F-1 functions to regulate apoptosis and to suppress cell proliferation...

....

Various types of cancers are generated through mutations or dysregulations of oncogenes/tumor suppressor genes involved in cell cycles and signaling transduction pathways...

..Gene expression profiling may be useful in examining differences underlying age- and sex-specific outcomes in non-small cell lung cancer (NSCLC)...

Tumors can become dependent upon signaling by oncogenes. In a recent issue of Cancer Cell, Sharma et al...

..In this paper we hypothesized that disturbed alternative splicing in ccRCC may result from improper expression of splicing factors, mediators of splicing reactions...

Identification of novel oncogenes and tumor suppressors in hepatocellular carcinoma (HCC) is challenging, both because of the tumor complexity and the difficulty in integrating the very large amount of data provided by different ..

..The database is designed in order to aid the synthesis of siRNAs, which target human oncogenes (OsiRNAs)...

..This newly discovered Wnt family member was expressed in the embryo and mammary gland of virgin but not pregnant mice and represents a candidate collaborating oncogene of int-2/Fgf-3 in the mammary epithelium...

..The first subset of genes is frequently mutated across samples and tumor types, and includes well-studied oncogenes and tumor suppressor genes, such as members of the RAS, AKT and TP53 families, whose direct targeting has so far ..

The receptor-type oncogenes c-erbB2/neu and c-erbB have been found amplified and/or overexpressed in a number of tumours of epithelial origin. We have studied the expression of oncogenes in biopsies from human thyroid tumours...

..The present review describes the catalog of known genetic alterations and the recent advances in global expression profiles in lung tumors and briefly discusses their use in clinical management...

..The frequently mutated genes are well-known oncogenes and tumor suppressors that are involved in generic processes of cell-cycle control, signal transduction, and ..

..Many recurrently amplified oncogenes were previously known to be activated only by disease-specific translocations...

..A second order sensitivity analysis scheme is additionally used to determine the effect of correlations among mutations at different sites in the pathways...

..Our results showed that miR-16, miR-34a-c, miR-17-5p and miR-125 were up-regulated, and their associated oncogenes (BCL2, E2F1 and E2F3, respectively) were down-regulated after cisplatin treatment...

..These results implicate ROCK-mediated ezrin C-terminal phosphorylation in transformation by RhoGEFs...

..The aim of the study was to compare the expression level of mammalian target of rapamycin (mTOR) tumor suppressor and oncogene-related genes in the endometrium of women with and without endometriosis as well as in ovarian endometriosis...

..mRNA for the metalloproteases stromelysin (MMP-3) and type I collagenase (MMP-1), which are often induced by oncogenes and growth factors and have been implicated in tumor invasiveness, cannot be induced by epidermal growth factor ..

..Specific examples of altered ETS factor expression are highlighted, and therapeutic technologies that may be used to target ETS factors and their cofactors and downstream target genes in prostate cancer are discussed...

According to classical concepts of viral oncogenesis, the persistence of virus-specific oncogenes is required to maintain the transformed cellular phenotype...

..In this paper we have investigated STAT3 involvement in signalling induced by TRK oncogenes. We showed that TRK oncogenes trigger STAT3 phosphorylation both on Y705 and S727 residues and STAT3 ..

..We also consider the clinical relevance of this by examining the role of E2F1 as a prognosis factor and as a target for the development of novel strategies...

This review discusses the dosage effects of some oncogenes in leukemogenesis and compares various methods that model human hematologic malignancies in mice by introducing genetic lesions in a cell type-specific, time-controlled, and ..

..their paradoxical effects in cancer, in which they can function either as tumour-suppressor genes or dominant oncogenes according to context...

..This work raises several important questions: Can other miRNAs act as tumor suppressors or oncogenes? Is miRNA deregulation a critical aspect of tumor development and maintenance? A number of recent studies have ..

..CONCLUSION: Several types of genetic damage occur in cancer cells: activation of protooncogenes into oncogenes that give cells an abnormal growth advantage; inactivation of tumor suppressor genes that would normally slow or ..

..II. Tumors with phenotypic quantitative or qualitative changes of the NMP spectrum...

..The underlying disease mechanisms remain unclear, but tumor suppression genes (p53, p16, APC) and, oncogenes (K-ras, cyclin D1, c-erb-2) seem to cause the malignant transformation of Barrett's esophagus, and the genetic ..

..A far reaching goal is the computer representation of multiple molecular components and their interactions, "E-cell in cyberspace", in which prognostic behaviour and therapeutic responsiveness can be approximately predicted...

Cancer development and progression involve activation of multiple oncogenes and inactivation of multiple tumor suppressor genes...

..We are aiming at developing a PCR approach to differentiate between the forms of PDCD2 found in normal bone marrow and blood, and the PDCD2 forms associated with leukemic cells. ..

..We are aiming at developing a PCR approach to differentiate between the forms of PDCD2 found in normal bone marrow and blood, and the PDCD2 forms associated with leukemic cells. ..

....

....

..This model may be used to study the role that Cul4A plays in mesothelioma carcinogenesis, and may also be potentially useful for further drug discovery, e.g., to screen for molecules that inhibiting Cul4A-mediated p21 degradation. ..

..instability pathway, involving alterations in key tumor suppressor genes (APC and p53, but also SMAD4) and oncogenes (especially Ras, but also EGFR, c-myc, B-Raf) and their downstream effectors...

The protein products of a number of retroviral oncogenes and growth factor receptors are protein tyrosine kinases...

..instability pathway, involving alterations in key tumor suppressor genes (APC and p53, but also SMAD4) and oncogenes (especially Ras, but also EGFR, c-myc, B-Raf) and their downstream effectors...

..instability pathway, involving alterations in key tumor suppressor genes (APC and p53, but also SMAD4) and oncogenes (especially Ras, but also EGFR, c-myc, B-Raf) and their downstream effectors...

..c-abl proteins contain a tyrosine kinase domain which is essential to the transforming function of c-abl derived oncogenes. The ubiquitous expression of the c-abl gene suggests that it may serve a function common to all cells...

We have conducted a two-species pilot screen to discover new oncogenes and tumor suppressor genes that can drive prostate cancer initiation and/or progression in mice and humans...

..Our long-term, ultimate goal is to use localization controllable versions of Bcr-Abl (as gene therapy) for treatment of CML. ..

..Our long-term, ultimate goal is to use localization controllable versions of Bcr-Abl (as gene therapy) for treatment of CML. ..

..The tumors formed by each combination of oncogenes also grow at equivalent rates although those formed by H-ras plus ElA appear to be encapsulated...

....